慢性肝疾患で産生される自己抗体が血小板減少を誘導する機序の解明

阐明慢性肝病中产生的自身抗体引起血小板减少的机制

• 批准号: 22K08017
• 负责人: 佐藤 隆司
• 金额: $ 2.66万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22K08017/
• 关键词: 慢性肝疾患; 血小板減少; 自己抗体; 自己免疫

慢性肝疾患における血小板減少の病因を解明するために、抗血小板抗体を含めた自己抗体が血小板減少に与える影響について検討した。本研究では、重度の血小板減少を伴う肝硬変(LC)患者、一次性免疫性血小板減少症(ITP)患者および健常人を対象とした。ELISPOT法により抗GPIIb/IIIa抗体産生B細胞数、ELISAにより血漿中の抗GPIIb/IIIa抗体、B細胞活性化因子(BAFF)濃度、増殖誘導リガンド(APRIL)濃度、フローサイトメトリによりB細胞サブセット分画および制御性T細胞(Treg)を測定し、比較した。抗GPIIb/IIIa抗体産生B細胞数は、ITP患者および健常人と比べ、LC患者で有意に多かった (p<0.001)。血小板関連抗GPIIb/IIIa抗体は、ITP患者および健常人と比べ、LC患者で有意に高かった(p<0.01)。 血漿BAFF濃度はITP患者および健常人と比べ、LC患者で有意に高く(p<0.01)、血漿APRIL濃度は健常人と比べ、LC患者で有意に高かった(p<0.001)。LC患者において、抗GPIIb/IIIa抗体産生B細胞数および血小板関連抗GPIIb/IIIa抗体は、血漿BAFF濃度と正の相関が認められた。LC患者では健常人と比べ、ナイーブB細胞と形質芽細胞が多く（p=0.005、p=0.03）、形質芽細胞は血漿BAFF濃度と正の相関が認められた。LC患者は、ITP患者および健常人と同様のTreg数であり、差は認められなかった。血小板減少を伴うLC患者では、過剰なBAFF産生により、抗GPIIb/IIIa抗体を産生するB細胞が多くなることが想定され、血小板減少と自己免疫が関連している可能性が示唆された。

The causes of chronic liver disease, thrombocytopenia, and thrombocytopenia are explained, and anti-platelet antibodies are self-antibodies, and thrombocytopenia and their effects are clarified. This study was conducted on patients with severe thrombocytopenia and liver cirrhosis (LC), and patients with one-time immune thrombocytopenia (ITP). ELISPOT method measured the number of B cells producing anti-GPIIb/IIIa antibodies, ELISA measured anti-GPIIb/IIIa antibodies in plasma, and B cell activating factor (BAF) F) Concentration, proliferation inducing PRIL concentration, FPRIL concentration B-cell classification and control T-cell (Treg) measurement and comparison. The number of anti-GPIIb/IIIa antibody-producing B cells was lower than that of normal people in ITP patients and higher in LC patients (p<0.001). Platelet-related anti-GPIIb/IIIa antibodies were higher than those of normal people in ITP patients and higher in LC patients (p<0.01). Plasma BAFF concentration was higher than that of normal people in ITP patients and higher in LC patients (p<0.01). Plasma APRIL concentration was higher than that of normal people in ITP patients and higher in LC patients (p<0.001). In LC patients, there is a positive correlation between the number of B cells producing anti-GPIIb/IIIa antibodies, platelet-associated anti-GPIIb/IIIa antibodies, and plasma BAFF concentration. In LC patients, there is a positive correlation between the ratio of B cells and germ cells in healthy people (p=0.005, p=0.03) and the concentration of plasma BAFF in germ cells. LC patients and ITP patients have the same number of Treg as normal people and the same number of Tregs as normal people, and the number of different Tregs is the same as that of normal people. Thrombocytopenia is associated with LC patients, and BAFF-producing patients, and anti-GPIIb/IIIa antibodies are produced. There are too many B cells and there is a possibility that there is a link between thrombocytopenia and autoimmunity.

项目成果

B cell-activating factor is involved in thrombocytopenia in patients with liver cirrhosis

• DOI: 10.1007/s00277-022-04973-x
• 发表时间: 2022-09
• 期刊: Annals of Hematology
• 影响因子: 3.5
• 作者: T. Satoh;Hayato Takiguchi;H. Uojima;M. Kubo;Chisato Tanaka;Fumiko Yokoyama;Naohisa Wada;K. Miyazaki;H. Hidaka;Chika Kusano;M. Kuwana;R. Horie

Introduction of direct-acting antiviral agents alters frequencies of anti-GPIIb/IIIa antibody-producing B cells in chronic hepatitis C patients with thrombocytopenia

• DOI: 10.1080/09537104.2022.2161498
• 发表时间: 2023-12-31
• 期刊: PLATELETS
• 影响因子: 3.3
• 作者: Satoh，Takashi;Uojima，Haruki;Horie，Ryouichi
• 通讯作者: Horie，Ryouichi